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通过生物信息学方法鉴定与急性 A 型主动脉夹层相关的分子机制。

Identification of the molecular mechanisms associated with acute type A aortic dissection through bioinformatics methods.

机构信息

Cardiovascular Department, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Braz J Med Biol Res. 2019 Nov 7;52(11):e8950. doi: 10.1590/1414-431X20198950. eCollection 2019.

Abstract

Aortic dissection is characterized by the redirection of blood flow, which flows through an intimal tear into the aortic media. The purpose of this study was to find potential acute type A aortic dissection (AAAD)-related genes and molecular mechanisms by bioinformatics. The gene expression profiles of GSE52093 were obtained from Gene Expression Omnibus (GEO) database, including 7 AAAD samples and 5 normal samples. The differentially expressed genes (DEGs) were detected between AAAD and normal samples. The functional annotation and pathway enrichment analysis were conducted through the Database for Annotation, Visualization and Integration Discovery (DAVID). A protein-protein interaction network was established by the Search Tool for the Retrieval of Interacting Genes (STRING) software. The microRNAs (miRNAs) of these differentially expressed genes were predicted using <microRNA.org> database. Moreover, DEGs were analyzed in the comparative toxicogenomics (CTD) database to screen out the potential therapeutic small molecules. As a result, there were 172 DEGs identified in patients with AAAD. These DEGs were significantly enriched in 6 pathways, including cell cycle, oocyte meiosis, DNA replication, extracellular matrix-receptor interaction, and mineral absorption pathway. Notably, CDC20, CDK1, CHEK1, KIF20A, MCM10, PBK, PTTG1, RACGAP, and TOP2A were crucial genes with a high degree in the protein-protein interaction network. Furthermore, potential miRNAs (miR-301, miR-302 family, and miR-130 family) were identified. In addition, small molecules like azathioprine and zoledronic acid were identified to be potential drugs for AAAD.

摘要

主动脉夹层的特征是血流方向发生改变,血液通过内膜撕裂进入主动脉中层。本研究旨在通过生物信息学寻找潜在的急性 A 型主动脉夹层(AAAD)相关基因和分子机制。从基因表达综合数据库(GEO)中获取了 GSE52093 的基因表达谱,包括 7 个 AAAD 样本和 5 个正常样本。检测 AAAD 和正常样本之间的差异表达基因(DEGs)。通过数据库检索进行基因交互(STRING)软件建立蛋白质-蛋白质相互作用网络。通过 <microRNA.org> 数据库预测这些差异表达基因的 microRNAs(miRNAs)。此外,在比较毒理学基因组学(CTD)数据库中分析 DEGs,以筛选出潜在的治疗性小分子。结果,在 AAAD 患者中鉴定出 172 个 DEG。这些 DEG 显著富集在 6 条通路中,包括细胞周期、卵母细胞减数分裂、DNA 复制、细胞外基质-受体相互作用和矿物质吸收途径。值得注意的是,CDC20、CDK1、CHEK1、KIF20A、MCM10、PBK、PTTG1、RACGAP 和 TOP2A 是蛋白质-蛋白质相互作用网络中具有高连接度的关键基因。此外,还鉴定出了潜在的 miRNAs(miR-301、miR-302 家族和 miR-130 家族)。此外,还鉴定出了潜在的小分子,如硫唑嘌呤和唑来膦酸,它们可能是 AAAD 的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f816/6853077/57f30e8579b9/1414-431X-bjmbr-52-11-e8950-gf001.jpg

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